In the present investigation, the Prenatal Factors and Bipolar Disorder (PFB) Project, we shall examine the relationship between early developmental insults and risk of adult bipolar affective disorder. Bipolar disorder is a highly disabling psychiatric illness. Despite considerable research, its etiologies are not well understood, in part due to a lack of rigorous epidemiologic studies. In the PFB study, we aim to better understand early developmental risk factors for bipolar disorder, and assess whether these factors are specific to schizophrenia. For this purpose, we shall utilize the birth cohort of the Child Health and Development Study, a large and representative sample of births in the Oakland, California area. The study features numerous strengths, including a rich array of prospectively collected data beginning in the prenatal period, and archived maternal serum samples, which were stored frozen in nearly all pregnancies. We have previously conducted a follow-up investigation of schizophrenia in this cohort, which has yielded several intriguing findings on the relationship between in utero exposures and risk of that disorder. We aim to: 1) Examine the relationship between in utero infectious and immunologic exposures that can be assayed using archived prenatal serum specimens, and risk of bipolar disorder. These exposures include prenatal influenza and toxoplasmosis infection, and cytokine elevations; 2) examine the relationship between early developmental non-infectious factors and bipolar disorder. These factors include elevated maternal body mass index, maternal smoking and alcohol use, intrauterine growth retardation, and gestational age. 3) Assess pathways that may mediate observed associations between early developmental exposures and risk of bipolar disorder. We shall diagnose cases of bipolar disorder in the cohort using a structured interview, and use both nested case-control and cohort analyses to assess the relationship between the elaborated early developmental exposures and bipolar disorder. These study aims should enable us to identify important causes of bipolar disorder. This would have implications for developing strategies for the prevention of bipolar disorder by elimination or reduction of the identified risk factors, facilitate our understanding of the pathogenesis of bipolar disorder, and ultimately reveal susceptibility genes that interact with the risk factors. [unreadable] [unreadable]